The basic defect(s) in Cystic Fibrosis (CF) still remains unknown. There is no reliable test or assay for carriers of the CF gene which is inherited in an autosomal recessive fashion. We have developed an in vitro bioassay using the ciliated, mucus secreting, free-swimming urn cell complex (UCC) obtained from the coelomic cavity of the marine invertebrate Sipunculus nudus. Sera from patients with CF (homozygotes) and sera from their parents (heterozygotes) have quantitatively greater mucus stimulating substances (MSS) detected in the UCC bioassay than sera from controls, including controls with a variety of diseases. Preliminary data indicate that MSS in CF sera is chromatographically different than the quantitatively lower amount of MSS in control sera. The proposed investigations were designed to further isolate and purify MSS from the sera of patients with CF, their parents, and controls. These purified MSS can then be characterized and compared to each other immunochemically, chemically and biologically. The knowledge gleaned from these studies may shed light on the basic defect(s) in CF. This information could lead to better treatment and therapy for CF patients (heterozygotes do not exhibit any symptoms of the disease). Furthermore, with purified MSS in hand, an electrophoretic and/or immunologic assay can be developed. Availability of such an assay should then allow fast and reliable detection of heterozygotes.